Severe Fistulizing Crohn's-Like Disease in a Patient With Common Variable Immunodefficiency

Background:
Common variable immunodeficiency (CVID) is a heterogenous primary immune disorder characterized by hypogammaglobulinemia and impaired production of specific immunoglobulin with different clinical manifestations (infections, asthma and other allergic/autoimmune diseases, enteropathy, lymphoproliferative, malignancies). There are reports of inflammatory bowel diseases in CVID, with incidence in range of 2-4%. While immunoglobulin replacement therapy is the elementary therapeutic intervention in CVID, azathioprine and anti-TNF treatment is standard of care in Crohn’s disease.
Methods:
A 35-year-old woman with CVID diagnosed 20 years earlier was hospitalized in gastroenterology department for exacerbations of Crohn’s like disease (up to 15 blood-stained bowel movements daily, active perianal fistulas, left labial abscess with fecal discharge from the vagina). C-reactive protein level was 78.0 mg/L, stool calprotectin 1516 ug/g, HGB level 10.5 g/dL, MCV 70 fl, iron level 14 ug/dL. The patient manifested leucopenia, hypoalbuminemia, hypoproteinemia, decreased concentrations of immunoglobulins: IgA < 5.0 g/L, IgM < 5.0 g/L and IgG 337 g/L. The patient was cachectic (BMI 16 kg/m2). We observed massive hemorrhage from the lower gastrointestinal tract and fistulas (decrease in HGB to 5.6 g/dL). In the CT scan thickened and contrast enhanced wall of terminal ileum, sigmoid colon and rectum was found as well as inflammatory infiltrates and abscesses in the perineal region. Abscesses were surgically managed (incision and drainage). Colonoscopy with ileoscopy showed ulcers in the colon and cobblestone pattern of mucosa in the ileum. Repeated blood and urine microbiological cultures were negative. Stool examination for enteric pathogens and parasitic ova were negative. Latent tuberculosis was excluded. Serological analysis excluded hepatitis B, C and HIV viral infections, but we found in blood 3689 copies/mL of CMV-DNA. The pathological examination of large bowel biopsies confirmed cytomegalovirus infection. The patient was treated with antibiotics, ganciclovir, systemic steroids and transfusions of packed red blood cells. Immunoglobulins were administered, and protein and electrolyte deficiencies corrected. The management was determined by the multidisciplinary team (gastroenterologist, immunologist, surgeon, gynecologist). Due to CVID, leucopenia, CMV infection, recurrent difficult-to-treat abscesses the use immunosuppressants and TNF inhibitors was rejected, but owing to entero-vaginal fistula and significant fecal discharge from large-sized perianal fistulas the surgical treatment was decided (laparoscopy, loop ileostomy – 07.2023).
Results:
On follow-up (08.2023 – 08.2024) the patient’s condition gradually improved, the fistulas healed. Currently the patient is well-nourished without anemia, she continues immunoglobulin replacement therapy.
Conclusions:
We present an unusual case of CVID with delayed development of severe fistulizing Crohn’s-like disease, ineffectively treated with antibiotics. This case shows that Crohn’s’ like disease may develop in setting of humoral immune failure, in which ileostomy may be effective treatment option when immunosuppressants and biologics cannot be safely used.